Part 7

Hillebrand[182] has called attention to the fact that the igneous rocks of the Rocky Mountains showed a higher percentage of barium than rock from other portions of the United States, so that under these conditions one might expect the presence of barium in plants growing in this region. A sample of _Aragallus lamberti_ and one of _Astragalus mollissimus_ were sent to the Bureau of Chemistry for spectroscopic examination for various elements and they reported traces of barium in each.[183]

With these arguments the writer felt sure of the presence of barium, and the matter was discussed with Dr. E. C. Sullivan, of the United States Geological Survey, and he kindly corroborated the conclusions reached as to the presence of barium, controlling its presence by means of the spectroscope, and estimated it roughly as 0.1 per cent BaO in the ash of a sample of _Aragallus lamberti_ (6.3 milligrams BaSO_{4} in 4 grams ash). This determination was made by Hillebrand's method.

Kobert has anticipated this result, saying that "all plants are in the position occasionally to take up barium combinations from the soil," and "the plants which thus contain barium may act injuriously to men and animals."[184]

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FOOTNOTES:

[161] Swain, R. E., and Harkins, W. D. Arsenic in Vegetation Exposed to Smelter Smoke. Journ. Amer. Chem. Soc., vol. 30, p. 915. 1908.--Harkins, W. D., and Swain, R. E. The Chronic Arsenical Poisoning of Herbivorous Animals. Journ. Amer. Chem. Soc., vol. 30, p. 928, 1908.

[162] A similar extract was sent to the Bureau of Chemistry, and that Bureau also reported an absence of the elements of the H_{2}S group.

[163] Bachem, C. Pharmakologisches über einige Edelerden. Arch. Internat. de Pharmacodyn., vol. 17, p. 363. 1907.

[164] Sestini, F. Esper. di Vegetaz. del Frumento con Sostituz. della Glucina alla Magnesia. Staz. Sper. Agrar. Ital., vol. 20, p. 256. 1891.--Di alcuni Elementi Chimici Rari a Trovarsi nei Vegetabili. Staz. Sper. Agrar. Ital., vol. 15, p. 290. 1888.

NOTE.--The ammonium sulphid precipitate was very small if the phosphates were first removed with tin and nitric acid.

[165] Böhm, C. R. Darstellung d. seltenen Erden, vol. 1, p. 40. 1905.

[166] Wait, C. E. Occurrence of Titanium. Journ. Amer. Chem. Soc., vol. 18, p. 402. 1896.

NOTE.--There seem to be no records of any study of the pharmacological action of titanium.

[167] Compare Jaksch, R. v. Ueber Mangantoxikosen und Manganophobie. Münch. Med. Woch., p. 969. 1907.

[168] Wohlwill, F. Ueber d. Wirkung d. Metalle d. Nickelgruppe. Arch. f. Exper. Path., vol. 56, p. 409. 1907.

[169] Laband, L. Zur Verbreitung des Zinkes im Pflanzenreiche. Zeits. f. Untersuch. d. Nahrungs u. Genussmittel, vol. 4, p. 489. 1901.

[170] Cæsium occurs in various plants and the possibility of poisoning by this element must be considered. It is hoped that the writer may be able to undertake a more thorough pharmacological study of this element.

[171] Acqua, C. Sull'accumulo di Sostanze Radioattive nei Vegetali. Atti della Reale Accad. dei Lincei, 5 s, vol. 16, sem. 2, p. 357. 1907.

[172] Compare Meltzer, S. J. Toxicity of Magnesium Nitrate When Given by Mouth. Science, vol. 26, p. 473. 1907.

[173] Burgassi, G. Modificaz. del Ricambio per Azione dello Stronzio. Archiv. di Farmacol., vol. 6, p. 551. 1907.

[174] Noyes, A. A., and Bray, W. C. System of Qualitative Analysis for the Common Elements. Journ. Amer. Chem. Soc., vol. 29, pp. 168, 172, and 191. 1907.

NOTE.--Barium sulphate is nontoxic on account of its insolubility. Orfila fed 16-24 grams to dogs without causing any disturbance. Bary, A. Beitr. z. Baryumwirkung. Dorpat, 1888, p. 25.

[175] Sprengel, C. Von den Substanzen der Ackerbrume und des Untergrundes, Journ. f. Techn. u. OEkon. Chem., vol. 3, p. 313. 1828.

[176] Eckard, G. E. Baryt, ein Bestandtheil der Asche des Buchenholzes. Annal. der Chem. u. Pharm., n. s., vol. 23, p. 294. 1856.

[177] Forchhammer, J. G. Ueber den Einfluss des Kochsalzes auf die Bildung der Mineralien. Annal. d. Physik u. Chemie, vol. 5, p. 91. 1905.--Lutterkorth, H. Kohlensäurer Baryt, ein Bestandtheil des Sandsteines in der Gegend von Göttingen. Annal. d. Chem. u. Pharm., n. s., vol. 23, p. 296. 1856.

[178] Dworzak, H. Baryt unter den Aschenbestandtheilen des. Ægyptischen Weizen. Landw. Versuchs.-Stat., vol. 17, p. 398. 1874.

[179] Knop, W. Analysen von Nilabsatz. Landw. Versuchs.-Stat., vol. 17, p. 65. 1874.--Compare also Demoussy, E., Absorption par les Plantes de Quelques Sels Solubles, Thése, Paris, 1899.--Knop, W., Einige neue Resultate der Untersuchung über die Ernährung der Pflanze, Ber. ü. Verhandl. d. königl. sächs. Gesells. d. Wissens. zu Leipzig, Math. Phys. Cl., vol. 29, p. 113, 1877.--Suzuki, U., Can Strontium and Barium Replace Calcium in Phænogams? Bul. Coll. Agric. Tokio Imp. Univ., vol. 4, p. 69, 1900-1902.

[180] Hornberger, R. Ueber d. Vorkommen d. Baryums in d. Pflanze und im Boden. Landw. Versuchs.-Stat., vol. 51, p. 473. 1899.

[181] Roscoe, H. E., and Schorlemmer, C. Treatise on Chemistry, vol. 2, p. 455. 1897.

[182] Hillebrand, W. F. Analysis of Silicate and Carbonate Rocks. Dept. Interior, U. S. Geol. Survey, Bul. 305, p. 18. 1907.

[183] This report came from the Plant Analysis Laboratory of the Bureau of Chemistry, a different one from that which later controlled the writer's tests quantitatively and qualitatively. In other words, the conclusions of the writer as to the presence of barium were controlled by three separate individuals.

[184] Kobert, R. Kann ein in einem Pflanzenpulver gefundener abnorm höher Barytgehalt erklärt werden durch direkte Aufnahme von Baryumsalze durch die lebende Pflanze aus dem Boden? Chem. Zeit., vol. 10, p. 491. 1899.

NOTE.--The writer has also found barium in entirely different botanical families from the loco-weed, and it is hoped a report can shortly be made of some of these.

NOTE.--The first sample of ash analyzed by the Bureau of Chemistry had 0.21 per cent Fe_{2}O_{3}, 0.92 per cent Al_{2}O_{3}, 0.98 per cent CaO, 0.37 per cent MgO, 5.50 per cent SiO_{2}. The second lot was only examined for certain constituents, and gave K_{2}O, 2.25 per cent; CaO, 1.20 per cent; MgO, 0.41 per cent; P_{2}O_{5}, 0.52 per cent; and SO_{3}, 0.24 per cent.

=TOTAL ASH DETERMINATIONS OF LOCO PLANTS.=

The reports of the ash analyses of the loco plants show marked variations in the total amount of the ash. Thus, from _Aragallus lamberti_ Dyrenforth obtained 4.32 per cent and O'Brine 13.52 per cent of ash. The Bureau of Chemistry analyzed two different samples of this dried plant and reported in one case 11.15 per cent and in the second 11.64 per cent of ash. O'Brine[185] obtained 13.52 per cent of ash from the same species. The writer's analysis[186] gave in one sample of _Aragallus lamberti_, collected at Hugo, Colo., in 1907, 18.8 per cent of ash; a second lot (1907), 12.44 per cent; a third (1906), 11 per cent, and a fourth (May, 1905) gave 37.3 per cent of ash.[187] One lot from Woodland Park, Colo. (October, 1906), gave 6.4 per cent. One lot from Hugo, Colo. (October, 1907), yielded 9.6 per cent.

In the case of _Astragalus mollissimus_, Wentz obtained 6.76 per cent, Sayre 12.01 per cent, Kennedy 20 per cent, O'Brine 12.15 per cent, while the sample analyzed by the Bureau of Chemistry gave 18.4 per cent of ash. One sample from Kit Carson County, Colo. (December, 1906), which proved inactive physiologically, gave an ash content of 6.9 per cent. A sample of _Astragalus missouriensis_ collected at Hugo, Colo., June, 1907, yielded an ash content of 21.8 per cent, and an _Astragalus missouriensis_ collected at Pierre, S. Dak., September, 1907, yielded 27 per cent. An _Astragalus nitidus_ from Custer, S. Dak. (July, 1907), gave 5.2 per cent ash, while an _Astragalus nitidus_ collected at Woodland Park, Colo., in October, 1906, yielded 7.8 per cent, and another specimen of _Astragalus nitidus_ also collected at Woodland Park, Colo., in October, 1907, gave 12.2 per cent. An _Astragalus drummondii_ from Custer, S. Dak. (July, 1907), gave 5.9 per cent. _Astragalus pectinatus_ (Hugo, June, 1907) yielded 6.1 per cent. A fresh (undried) specimen of _Astragalus mollissimus_ (unknown origin, November, 1907) yielded 3.8 per cent of ash. One sample of _Astragalus decumbens_ (Ephraim, Utah, August, 1907) gave 21.8 per cent of ash.

These determinations must necessarily be only approximate, as the plants were collected by different persons who exercised different degrees of care in freeing them from adherent soil, and possibly in drying the plants, so that the main value of these figures is their aid in determining the amount of barium present.

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FOOTNOTES:

[185] The detailed analysis of O'Brine can be found on page 32 of this report.

[186] All ash and barium determinations were made from the dried plants save when otherwise specified.

[187] Evidently these plants must have been imperfectly freed from soil.

=BARIUM DETERMINATIONS IN THE ASH OF LOCO PLANTS.=

Attention has been called to the fact that in ashing plants containing barium a part at least of this barium is converted into the insoluble sulphate and a part into the carbonate, so that the characteristic pharmacological action of the ash will depend not upon the total barium present, but upon the form in which it occurs--little action if much BaSO_{4}, and more complete if more BaCO_{3} results. A further difficulty in the recognition of barium in plants is due to the fact that certain inorganic salts interfere with the precipitation by H_{2}SO_{4}.

A specimen of _Aragallus lamberti_ (Hugo, summer of 1907) with 12.44 per cent of ash was examined for its barium content by Hillebrand's method.[188] The method was as follows:

Two grams of the ash were first fused with sodium carbonate and the fused mass washed with water containing sodium carbonate. The residue was washed into a beaker and treated with a few drops of sulphuric acid. The residue now remaining was filtered and after ignition was treated with hydrofluoric and sulphuric acids. After evaporating off these acids, the residue was treated with sulphuric acid water, filtered, and then fused with sodium carbonate. After extracting with sodium carbonate water, the residue was dissolved in just enough hydrochloric acid and precipitated with sulphuric acid. The precipitate was dissolved in concentrated sulphuric acid and reprecipitated by water and weighed as BaSO_{4}.[189] So far as the writer can ascertain, there have been no control experiments made for this method to determine the experimental error.

Of the above ash, 1.998 grams gave 5.2 milligrams of BaSO_{4}, which would correspond to 75.75 milligrams of barium acetate crystals-- Ba(C_{2}H_{3}O_{2})_{2}+H_{2}O--in 200 grams of the dried plant. The residue by the Hillebrand method after weighing was tested with the spectroscope and gave a bright spectrum for barium. The same ash was analyzed by the Bureau of Chemistry, using a shorter method, and they reported 2.7 milligrams of barium sulphate in 1.1217 grams of ash. A second sample collected earlier in the summer, with an ash content of 18.6 per cent, was shown to yield barium corresponding to 3.4 milligrams of BaSO_{4} in 2.5 grams of the ash.[190]

One lot of _Aragallus lamberti_ collected at Hugo, Colo., in May, 1905, and which gave an ash content of 37.3 per cent, was found to yield 3 milligrams of BaSO_{4} from 1.998 grams of ash, or 173.88 milligrams of Ba(C_{2}H_{3}O_{2})_{2}+H_{2}O in 200 grams of the dried plant, but this ash also contained 0.27 per cent of SO_{3}. The Bureau of Chemistry reported the barium to correspond to 2.9 milligrams of BaSO_{4} in 2.45 grams of the ash.

The _Astragalus missouriensis_ (Hugo, June, 1907), with an ash content of 21.8 per cent, gave 3 milligrams of BaSO_{4} in 2.01 grams of ash, or 76.58 milligrams of Ba(C_{2}H_{3}O_{2})_{2}+H_{2}O in 200 grams of the dried plant. The residue after weighing was tested spectroscopically and gave a bright barium spectrum.

The _Astragalus drummondii_ from Custer, S. Dak. (1906), _Astragalus mollissimus_ from Kit Carson County, Colo. (December, 1906), and _Astragalus nitidus_ from Woodland Park, Colo. (October, 1907), were reported by the Bureau of Chemistry to contain no barium.

The ash of the _Astragalus pectinatus_ (Hugo, June, 1907) was reported by the Bureau of Chemistry to show no barium on spectroscopic examination.

Two grams of active loco plant ash yielded from 5 to 6 milligrams of BaSO_{4}, but it can be easily seen that in multiplying this amount to correspond to 200 grams of the dried plant errors would be likely to arise, so that the whole amount of barium would not necessarily be accounted for.

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FOOTNOTES:

[188] Hillebrand, W. F. Analysis of Silicate and Carbonate Rocks. U. S. Geol. Surv. Bul. 305, p. 116. 1907. See also Folin, O., On the Reduction of Barium Sulphate in Ordinary Gravimetric Determinations, in Journ. Biol. Chem., vol. 3, p. 81. 1907.

[189] All the determinations of barium which resulted either positively or negatively were made with the same bottle of sodium carbonate and H_{2}SO_{4}, so that impurities in the chemicals were thus eliminated.

[190] Report from Bureau of Chemistry.

=ANALYSIS OF SOILS.=

One sample of the soil from near Hugo, Colo., from which the _Aragallus lamberti_ was collected, was examined by the Bureau of Soils, and that Bureau reported the absence of barium and zirconium, at least of any recognizable by the chemical methods used, so that it can not be said that the barium came from any soil accidentally mixed with the ash. Traces of titanium were, however, found. Evidently the plant must collect minimal quantities of these elements from the soil and store them.

The water from a well of an adjacent area was examined by the Bureau of Chemistry and reported to contain 37.4 parts of calcium and 13.7 parts of magnesium in one million, and that the water contained no barium.[191]

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FOOTNOTES:

[191] Barium has been found in well water in England. See Thorpe, T. E., Contribution to the History of the Old Sulphur Well, Harrogate, in Philos. Mag., 5 s., vol. 2, p. 50, 1876.

=FEEDING EXPERIMENTS WITH BARIUM SALTS ON ANIMALS IN THE LABORATORY.=

On these figures the writer took 0.2 gram of crystallized barium acetate c. p., using the acetate because acetic acid has been proved in certain loco plants by Power and Cambier, and after dissolving it in water fed it at 9.45 a.m. to a rabbit weighing 1,177 grams. The head soon fell forward so that the nose rested on the ground. At 10.58 a.m. the rabbit seemed unable to guide itself and would run into obstructions if forced to move. There was no diarrhea but it urinated several times. There was a peculiar tremor of the muscles noted. The animal would not startle by sudden noises and at 11.06 a.m. could be placed on its back with ease. The pupils appeared about normal. The whites of the eyes showed very prominently. At 11.35 a.m. the fore legs were paralyzed. The following morning the animal was dead, its weight being 1,120 grams. The heart was dilated; the stomach was not hemorrhagic, but rather pale.

A second rabbit, which weighed 1,630 grams, was fed with a solution of 0.5 gram of the same salt at 9.42 a.m. At 10.35 a.m. the animal passed soft stools and showed a marked disinclination to move, with evidence of pain. The diarrhea[192] became more marked and the animal's hind quarters were soiled with feces. At 10.48 a.m. there was marked incoordination of the limbs and inability to stand. Finally, at 10.56 a. m., convulsions began and the animal died at 11.02 a.m. The autopsy was made about two hours later. The animal was then rigid. The kidneys seemed rather congested. The intestines were relaxed; mesenteric vessels dilated. The pyloric region of the stomach appeared hemorrhagic.

A third rabbit, fed like the preceding with 0.5 gram of barium acetate, showed much the same result. In this case there was some retching, but the other symptoms were as above, the animal dying in one hour and five minutes. No hemorrhages were seen in the stomach walls. It was noted that after the administration of certain doses, 0.2 gram, there was no diarrhea.

On September 23, 1907, a rabbit weighing 1,757 grams was fed at 10.42 a. m. with 0.1 gram of the same barium acetate. The temperature at the time of feeding was 102.9°F. At 12.05 a.m. the animal urinated. Temperature, 101.4°F. On September 24 the animal weighed the same. Temperature at 10.55 a.m., 102.3°F. The same amount of barium was fed. At 3.40 p.m. the temperature was 102.5°F. On September 25 the animal weighed 1,800 grams. Temperature, 102.2°F. at 10.39 a.m. The dose of barium was repeated. At 3.55 p.m. the temperature was 101.4°F. On September 26 at 9.38 a.m. the temperature was 101.1°F., and again the barium was given. At 3.57 p.m. the temperature was 101.5°F. On September 27 the rabbit weighed 1,772 grams. The temperature at 9.53 a. m. was 102.3°F. The barium was fed for the fifth time. At 10.27 a.m. there were general convulsions. The eyes teared. At 10.32 a.m. soft stools appeared and the animal urinated. Stools were passed at various periods. At 11.30 a.m. there were no signs of pain on pinching the ear. At 11.58 a.m. the animal retched. The animal was lying with the fore legs wide apart and could not support itself. At 12.05 p.m. the temperature was 98°F. and the rabbit died shortly after.

The peritoneal cavity seemed normal. The small intestines were relaxed, while the mesenteric vessels were dilated. The kidneys seemed congested. The stomach walls were pink and in places covered with mucus. The heart was relaxed save the left ventricle, which seemed firm.

On September 23, 1907, a second rabbit, weighing 1,360 grams, was fed with a similar solution and the feeding was repeated at the same time the first rabbit was fed. On September 27 the animal weighed 1,416 grams. On this day a peculiar movement of the hind legs on jumping appeared, apparently due to an inability to draw the legs completely up, and the fore legs were spread wide apart, as if too weak to support the animal. The temperature had also fallen. On September 28 the animal had apparently recovered. Weight, 1,516 grams on October 21.

On September 23, 1907, a third rabbit, weighing 1,304 grams, was fed with 50 milligrams of barium acetate. This dose was repeated each time the other two rabbits were fed. On September 27 it weighed 1,304 grams. Marked muscular twitching appeared, with disinclination to move. Finally there were convulsions and paralysis of the limbs. No stools were seen. This animal lay quiet all night, apparently unable to move, and continued on its side until 3.15 p.m. on September 28, when it gradually recovered, weighing 1,346 grams on October 24.

On October 24, 1907, a rabbit weighing 1,346.5 grams was fed with a solution of 25 milligrams of crystallized barium acetate. On the next day the weight was 1,318 grams, and the dose was repeated. On October 26 it weighed 1,275.7 grams, and the dose was repeated; on October 30 it weighed 1,332 grams, and on October 31 its weight was 1,375 grams. The animal died at night on November 6; weight, 1,134 grams. The post-mortem examination, made with Dr. Meade Bolton, of the Bureau of Animal Industry, was negative save for the presence of necrotic tissue in one enlarged thyroid.

On October 24, 1907, a rabbit weighing 1,332 grams was fed with a solution of 25 milligrams of crystallized barium acetate. On the next day the animal weighed the same, and the dose was repeated. On October 26 it weighed 1,289 grams, and the same amount of barium was given. On October 28 the weight was 1,219 grams and two days later 1,289 grams.

On October 31, 1907, a rabbit weighing 723 grams was fed with a solution of 25 milligrams of barium acetate. This rabbit was fed in all nine times during a period of ten days. At the end of this time it weighed 779 grams and died six days later, weighing 723 grams. The post-mortem was negative.

A rabbit weighing 779 grams was also fed on October 31, 1907, with a similar amount of barium. This dose was repeated six times during an interval of eight days. At the end of that time the animal still retained its normal weight. On November 14, 1907, it weighed 709 grams, having lost 70 grams. Thus after daily doses of 0.1 gram of crystallized barium acetate no symptoms appeared until the fifth day, when death resulted. After the similar administration of 50 milligrams severe symptoms developed on the same day, but the animal recovered. After the administration of 25 milligrams on three successive days the animal died. In other cases of feeding 25 milligrams for several successive days, some lost weight and died; others merely lost in weight, but recovered.

Bary fed a rabbit weighing 0.9 kilogram a solution of 30 milligrams of barium chlorid on one day, on the second day 90 milligrams, and on the third day 30 milligrams. The only symptom noted was diarrhea. The animal died on the fifth day. In other words, after feeding small doses of barium salts for several days acute symptoms suddenly set in, showing a cumulative action. This cumulative action has been noted on man.[193]

Onsum[194] fed a medium-sized rabbit daily with small doses of barium carbonate, beginning with 20 milligrams. When the total amount reached 0.19 grams the rabbit died. The animal before death showed paralysis, respiratory disturbances, and fall in temperature. The sensibility of the cornea diminished, but the pupils responded to light. The stomach walls showed ecchymoses and the blood vessels of the brain, the spinal cord, and the abdominal vessels were dilated. Emboli in the pulmonary arteries were also noted.

In a rabbit the application of 0.66 gram of barium chlorid to a wound was followed in twenty minutes by convulsions, paralysis, and finally coma and death.[195]

Of barium nitrate 0.66 gram mixed with sugar and fed to a rabbit caused death in less than one hour, and 0.33 gram induced death in another rabbit in twenty-seven hours.[196]

Six grains (0.4 gram) of barium iodid fed in solution to a rabbit caused death the following day. On this day there were tremors of the neck and shoulders with convulsive movements of the limbs. There was also grinding of the teeth. "The mucous membrane of the stomach was rose-red at the cardia, and softened." Membranes of the cord and brain also were congested.[197]

For rabbits weighing 1,500 to 2,000 grams the lethal dose of barium chlorid on subcutaneous use is stated to be 0.05 to 0.06 grams.[198]

A rabbit weighing 1,106 grams was fed with a solution containing 50 milligrams of crystallized barium acetate c. p. and 50 milligrams of zirconium chlorid (pure). In fifty-seven minutes the animal showed difficulty in moving the fore legs, developing marked paralysis of the same about five hours later, and died the following morning--that is, twenty-two hours after feeding. The heart was found dilated, kidneys congested, stomach walls pink and covered in places with mucus and partly digested blood, and cerebral dural vessels dilated, but no clots were seen; bladder full.

Mixtures of 0.5 gram of calcium acetate and 50 milligrams of barium acetate failed to kill. Mixtures of titanium and barium were not tried, as no titanium salt soluble in water and of neutral reaction was accessible.